Platelets are essential in normal hemostasis to prevent hemorrhage. However, pathologic thrombosis occurs when circulating platelets become activated and aggregate into a platelet plug at the site of vessel injury, leading to vascular occlusion and life-threatening conditions such as myocardial infarction and stroke. According to the Centers for Disease Control and Prevention, about 715,000 people each year in the United States suffer from a heart attack and many more from strokes.
Several FDA-approved drugs exist in the market to prevent or treat pathologic thrombosis by targeting key pathways of platelet activation such as thromboxane A2 synthesis, ADP-mediated signaling and integrin αIIbβ3. These drugs include aspirin, ticlopidine, clopidogrel, prasugrel, abciximab, eptifibatide, tirofiban, dipyridamole, cilostazol, and ticagrelor. However, each of these drugs has its own limitations, including weak therapeutic effects (e.g., aspirin), multiple side effects (e.g., ticlopidine, cilostazol, prasugrel), patient-to-patient variability in response and slow onset of action (e.g., clopidogrel), and intravenous injection only (e.g., abciximab, eptifibatide, tirofiban) (Michelson, Hematology 2011, 62-69). Accordingly, there is a strong need to develop and identify new compounds and/or methods for prevention or treatment of pathologic thrombosis.